After South Carolina seceded from the Union, US Army Major Robert Anderson and eighty-five men under his command from the 1st US Artillery remained in Charleston, South Carolina. They were initially stationed in Fort Moultrie, but relocated to the much more defensible Fort Sumter under the cover of darkness on December 26, 1860. South Carolina had already seized a large number of forts, but Anderson decided to hold his ground.

South Carolina demanded that the forces withdraw from the fort, but President James Buchanan refused. Buchanan decided to attempt to resupply the forces by sending an unarmed merchant ship, the Star of the West, to the fort, but it was fired upon by shore batteries and retreated. The troops remained at the fort while South Carolina and the Confederacy formed in February of 1861 debated whether attacking it was justified. Some individuals felt that the fort was the property of South Carolina since it was in Charleston Harbor, but others, like Jefferson Davis, felt that attacking it would make the south seem like an aggressor and deter neutral states from supporting their cause.

In March, Brigadier General P.G.T. Beauregard was appointed commander of South Carolina's forces in the city of Charleston. He demanded that Anderson and his forces immediately surrender or withdraw from the fort and prevented any supplies from reaching the fort. Anderson and his troops were slowly running out of food, but refused to withdraw, instead focusing on drills and preparing for a potential battle. An interesting point is that Anderson served as Beauregard's artillery instructor at West Point and were in fact close friends separated by political conflict.

In early April, President Lincoln decided to try to resupply the fort, sending several merchant vessels under escort of the US Navy to Charleston. On April 6, 1861, he told Francis Pickens, Governor of South Carolina, "an attempt will be made to supply Fort Sumter with provisions only, and that if such attempt be not resisted, no effort to throw in men, arms, or ammunition will be made without further notice, [except] in case of an attack on the fort." The Confederate leaders met in Montgomery to discuss the issue, deciding on April 9th to attack Fort Sumter and force it to surrender prior to the arrival of the US Fleet. Confederate Secretary of State Robert Toombs was the sole opponent of the decision, stating that the attack "will lose us every friend at the North. You will wantonly strike a hornet's nest. ... Legions now quiet will swarm out and sting us to death. It is unnecessary. It puts us in the wrong. It is fatal."

Beauregard was subsequently ordered, "You will at once demand its evacuation, and if this is refused proceed, in such a manner as you may determine, to reduce it." On April 11th, Beauregard sent envoys to the fort to issue the ultimatum and Anderson refused, but conceded that "if you do not batter the fort to pieces about us, we shall be starved out in a few days." At 3:20 AM on April 12th, the Confederates told Anderson that they would open fire in an hour if he did not surrender.

At 4:30 AM on April 12, 1861, the first mortar round was fired and exploded over Fort Sumter. Soon a total of 43 cannon and mortars were firing on the fort from Fort Moultrie, Fort Johnson, and Cummings Point. Anderson did his best to avoid casualties by firing guns from lower levels of the fort, but it was designed to fight ships, not land-based artillery that could fire over its walls.

The guns on the lower levels of the fort could not fire indirectly and were thus largely incapable of attacking the neighboring Fort Moultrie. Additionally, a low supply of ammunition complicated the situation for Anderson and his men. The bombardment of Fort Sumter continued for thirty-four hours, destroying the fort's officer quarters and starting a large fire. The bombardment also felled the flagpole and an envoy was dispatched to determine if it indicated a surrender.

At 2:00 PM on April 13, 1861, Anderson agreed to end the fighting. Terms were drawn up for surrender and at 2:30 PM on April 14th, the Fort was surrendered to the Confederacy. Casualties consisted of five Union and four Confederate injuries, but no deaths. Anderson's only condition for withdrawal was a 100-gun salute to the United States, which was ceased after fifty shots due to an accidental death.

Following withdrawal, the Union troops boarded a Confederate steamer, which transported them to a Union steamer, the Baltic, which was outside the harbor. The steamer was escorted by the fleet that had intended to resupply the fort, with Anderson still carrying the Fort Sumter flag. The seizure of Fort Sumter was the first military action of the United States Civil War. Following the event, Northern States rallied behind Lincoln and the war went into full swing. Fort Sumter remained in Confederate hands for the remainder of the war, only surrendering to the Union after Lee and the Confederacy surrendered. On April 14, 1865, Anderson, now a Major General, personally raised the original Fort Sumter flag once again.